Inhibition of Ca-calpain signaling is a new mechanism using polysaccharide to prevent macrophage foam cell formation and atherosclerosis

• Published in: Food & function Vol. 14; no. 9; pp. 436 - 448
• Main Authors: Li, Xue-Ying, Kuang, Dan-Dan, Guo, An-Jun, Deng, Yuan-Yuan, Pan, Li-Hua, Li, Qiang-Ming, Luo, Jian-Ping, Zha, Xue-Qiang
• Format: Journal Article
• Published: 09.05.2023
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d2fo04099a

The Ca 2+ -calpain signaling plays a pivotal role in regulating the upstream signaling pathway of cellular autophagy. The aim of the current work was to investigate the role of Ca 2+ -calpain signaling in the regulation of macrophage autophagy by a Laminaria japonica polysaccharide (LJP61A) in Ox-LDL induced macrophages and high fat diet fed atherosclerotic mice. Results revealed that the LJP61A markedly decreased the levels of intracellular Ca 2+ , calpain1, calpain2 and their downstream effectors (Gsα, cAMP and IP3), and simultaneously enhanced autophagy activity and lipid metabolism, thereby reducing lipid accumulation in the Ox-LDL stimulated macrophages and lipid-laden plaques in atherosclerotic mice. Moreover, BAPTA-AM (a Ca 2+ chelator) and calpeptin (a calpain inhibitor) synergistically strengthened the beneficial effects of LJP61A on autophagy and lipid metabolism by decreasing the levels of intracellular Ca 2+ , calpain1, calpain2, and their downstream effectors (Gsα, cAMP and IP3) induced by Ox-LDL. These findings suggested that the LJP61A suppressed macrophage derived foam cell formation and atherosclerosis by modulating the Ca 2+ -calpain-mediated autophagy. The LJP61A suppressed macrophage foam cell formation and atherosclerotic progression by modulating Ca 2+ -calpain mediated autophagy inhibition.